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Gastroenterology Mar 2022Epidemiologic and murine studies suggest that dietary emulsifiers promote development of diseases associated with microbiota dysbiosis. Although the detrimental impact... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND & AIMS
Epidemiologic and murine studies suggest that dietary emulsifiers promote development of diseases associated with microbiota dysbiosis. Although the detrimental impact of these compounds on the intestinal microbiota and intestinal health have been demonstrated in animal and in vitro models, impact of these food additives in healthy humans remains poorly characterized.
METHODS
To examine this notion in humans, we performed a double-blind controlled-feeding study of the ubiquitous synthetic emulsifier carboxymethylcellulose (CMC) in which healthy adults consumed only emulsifier-free diets (n = 9) or an identical diet enriched with 15 g per day of CMC (n = 7) for 11 days.
RESULTS
Relative to control subjects, CMC consumption modestly increased postprandial abdominal discomfort and perturbed gut microbiota composition in a way that reduced its diversity. Moreover, CMC-fed subjects exhibited changes in the fecal metabolome, particularly reductions in short-chain fatty acids and free amino acids. Furthermore, we identified 2 subjects consuming CMC who exhibited increased microbiota encroachment into the normally sterile inner mucus layer, a central feature of gut inflammation, as well as stark alterations in microbiota composition.
CONCLUSIONS
These results support the notion that the broad use of CMC in processed foods may be contributing to increased prevalence of an array of chronic inflammatory diseases by altering the gut microbiome and metabolome (ClinicalTrials.gov, number NCT03440229).
Topics: Animals; Carboxymethylcellulose Sodium; Diet; Double-Blind Method; Dysbiosis; Emulsifying Agents; Feces; Female; Gastrointestinal Microbiome; Healthy Volunteers; Humans; Male; Metabolome; Mice
PubMed: 34774538
DOI: 10.1053/j.gastro.2021.11.006 -
Nature Mar 2015The intestinal tract is inhabited by a large and diverse community of microbes collectively referred to as the gut microbiota. While the gut microbiota provides...
The intestinal tract is inhabited by a large and diverse community of microbes collectively referred to as the gut microbiota. While the gut microbiota provides important benefits to its host, especially in metabolism and immune development, disturbance of the microbiota-host relationship is associated with numerous chronic inflammatory diseases, including inflammatory bowel disease and the group of obesity-associated diseases collectively referred to as metabolic syndrome. A primary means by which the intestine is protected from its microbiota is via multi-layered mucus structures that cover the intestinal surface, thereby allowing the vast majority of gut bacteria to be kept at a safe distance from epithelial cells that line the intestine. Thus, agents that disrupt mucus-bacterial interactions might have the potential to promote diseases associated with gut inflammation. Consequently, it has been hypothesized that emulsifiers, detergent-like molecules that are a ubiquitous component of processed foods and that can increase bacterial translocation across epithelia in vitro, might be promoting the increase in inflammatory bowel disease observed since the mid-twentieth century. Here we report that, in mice, relatively low concentrations of two commonly used emulsifiers, namely carboxymethylcellulose and polysorbate-80, induced low-grade inflammation and obesity/metabolic syndrome in wild-type hosts and promoted robust colitis in mice predisposed to this disorder. Emulsifier-induced metabolic syndrome was associated with microbiota encroachment, altered species composition and increased pro-inflammatory potential. Use of germ-free mice and faecal transplants indicated that such changes in microbiota were necessary and sufficient for both low-grade inflammation and metabolic syndrome. These results support the emerging concept that perturbed host-microbiota interactions resulting in low-grade inflammation can promote adiposity and its associated metabolic effects. Moreover, they suggest that the broad use of emulsifying agents might be contributing to an increased societal incidence of obesity/metabolic syndrome and other chronic inflammatory diseases.
Topics: Adiposity; Animals; Carboxymethylcellulose Sodium; Colitis; Diet; Emulsifying Agents; Feces; Female; Gastrointestinal Tract; Germ-Free Life; Inflammation; Intestinal Mucosa; Male; Metabolic Syndrome; Mice; Microbiota; Obesity; Polysorbates
PubMed: 25731162
DOI: 10.1038/nature14232 -
Journal of Visualized Experiments : JoVE Mar 2017Monolayer cell culture does not adequately model the in vivo behavior of tissues, which involves complex cell-cell and cell-matrix interactions. Three-dimensional (3D)...
Monolayer cell culture does not adequately model the in vivo behavior of tissues, which involves complex cell-cell and cell-matrix interactions. Three-dimensional (3D) cell culture techniques are a recent innovation developed to address the shortcomings of adherent cell culture. While several techniques for generating tissue analogues in vitro have been developed, these methods are frequently complex, expensive to establish, require specialized equipment, and are generally limited by compatibility with only certain cell types. Here, we describe a rapid and flexible protocol for aggregating cells into multicellular 3D spheroids of consistent size that is compatible with growth of a variety of tumor and normal cell lines. We utilize varying concentrations of serum and methyl cellulose (MC) to promote anchorage-independent spheroid generation and prevent the formation of cell monolayers in a highly reproducible manner. Optimal conditions for individual cell lines can be achieved by adjusting MC or serum concentrations in the spheroid formation medium. The 3D spheroids generated can be collected for use in a wide range of applications, including cell signaling or gene expression studies, candidate drug screening, or in the study of cellular processes such as tumor cell invasion and migration. The protocol is also readily adapted to generate clonal spheroids from single cells, and can be adapted to assess anchorage-independent growth and anoikis-resistance. Overall, our protocol provides an easily modifiable method for generating and utilizing 3D cell spheroids in order to recapitulate the 3D microenvironment of tissues and model the in vivo growth of normal and tumor cells.
Topics: Cell Aggregation; Cell Culture Techniques; Cell Line, Tumor; Humans; Methylcellulose; Serum; Spheroids, Cellular; Time Factors
PubMed: 28448014
DOI: 10.3791/55544 -
Materials (Basel, Switzerland) Sep 2021Chemical modification of cellulose offers routes for structurally and functionally diverse biopolymer derivatives for numerous industrial applications. Among cellulose... (Review)
Review
Chemical modification of cellulose offers routes for structurally and functionally diverse biopolymer derivatives for numerous industrial applications. Among cellulose derivatives, cellulose ethers have found extensive use, such as emulsifiers, in food industries and biotechnology. Methylcellulose, one of the simplest cellulose derivatives, has been utilized for biomedical, construction materials and cell culture applications. Its improved water solubility, thermoresponsive gelation, and the ability to act as a matrix for various dopants also offer routes for cellulose-based functional materials. There has been a renewed interest in understanding the structural, mechanical, and optical properties of methylcellulose and its composites. This review focuses on the recent development in optically and mechanically tunable hydrogels derived from methylcellulose and methylcellulose-cellulose nanocrystal composites. We further discuss the application of the gels for preparing highly ductile and strong fibers. Finally, the emerging application of methylcellulose-based fibers as optical fibers and their application potentials are discussed.
PubMed: 34576360
DOI: 10.3390/ma14185137 -
Advances in Colloid and Interface... Jun 2022Polymeric materials play a vital role in our daily life, but the growing concern for the environment demands economical and natural biopolymers that can be cross-linked... (Review)
Review
Polymeric materials play a vital role in our daily life, but the growing concern for the environment demands economical and natural biopolymers that can be cross-linked to create technologically innovative lightweight materials. Their cellular matrix with extreme flexibility makes them highly acceptable for application prospects in material science, engineering, and biomedical applications. Furthermore, their biocompatibility, mechanical properties, and structural diversity provide a gateway to research them to form technologically important materials. In the light of the same, the review covers cellulose derivatives. The first section of the study covers the general properties and applications of cellulose and its derivatives. Then, the biopolymers are characterised based on their dielectric properties, crystallinity, rheology, and mechanical properties. An in-depth analysis of the diffuse process of swelling and dissolution followed by a brief discussion on diffusion and diffusion of crosslinking has been done. The review also covers a section on swelling and swelling kinetics of carboxymethyl cellulose (CMC) and hydroxyethyl cellulose (HEC). The examination of all the aforementioned parameters gives an insight into the future aspects of the biopolymers. Lastly, the study briefly covers some preferred choices of cross-linking agents and their effect on the biopolymers.
Topics: Biopolymers; Carboxymethylcellulose Sodium; Cellulose; Hydrogels; Rheology
PubMed: 35483124
DOI: 10.1016/j.cis.2022.102681 -
International Journal of Biological... Jun 2022Thermal and rheological properties of methylcellulose (MC) and hydroxypropyl methylcellulose (HPMC) hydrogels with chitosan (CHI) were investigated to verify the...
Thermal and rheological properties of methylcellulose (MC) and hydroxypropyl methylcellulose (HPMC) hydrogels with chitosan (CHI) were investigated to verify the potential application of these blends as structured systems for oil transport (emulgel, oleogels, and bigels). FTIR confirmed hydrophobic interactions of cellulosic polymers with chitosan. In the temperature sweep, the thermosensitive hydrogels showed their reduced gel point compared to the original polymers. The gelation temperature was reduced from 66.9 °C for pure HPMC to 43.6 °C and 43.6 °C (MC pure polymer) to 39.3 °C when 30% CHI was added for both cases. The addition of 20 and 30% chitosan is enough to modify the extension of the gelation temperature of these polymers. These results indicate that the addition of chitosan enables MC and HPMC to form gels at lower temperatures, which could allow milder thermal conditions to be applied in processing oil carrier systems.
Topics: Chitosan; Hydrogels; Hypromellose Derivatives; Methylcellulose; Polymers; Rheology; Temperature
PubMed: 35413310
DOI: 10.1016/j.ijbiomac.2022.04.035 -
International Journal of Molecular... May 2021Rectal drug delivery is an effective alternative to oral and parenteral treatments. This route allows for both local and systemic drug therapy. Traditional rectal dosage... (Review)
Review
Rectal drug delivery is an effective alternative to oral and parenteral treatments. This route allows for both local and systemic drug therapy. Traditional rectal dosage formulations have historically been used for localised treatments, including laxatives, hemorrhoid therapy and antipyretics. However, this form of drug dosage often feels alien and uncomfortable to a patient, encouraging refusal. The limitations of conventional solid suppositories can be overcome by creating a thermosensitive liquid suppository. Unfortunately, there are currently only a few studies describing their use in therapy. However, recent trends indicate an increase in the development of this modern therapeutic system. This review introduces a novel rectal drug delivery system with the goal of summarising recent developments in thermosensitive liquid suppositories for analgesic, anticancer, antiemetic, antihypertensive, psychiatric, antiallergic, anaesthetic, antimalarial drugs and insulin. The report also presents the impact of various types of components and their concentration on the properties of this rectal dosage form. Further research into such formulations is certainly needed in order to meet the high demand for modern, efficient rectal gelling systems. Continued research and development in this field would undoubtedly further reveal the hidden potential of rectal drug delivery systems.
Topics: Acrylic Resins; Administration, Rectal; Alginates; Body Temperature; Drug Compounding; Drug Delivery Systems; Forecasting; Gels; Hot Temperature; Humans; Intestinal Absorption; Methylcellulose; Pharmaceutical Preparations; Poloxamer; Povidone; Suppositories
PubMed: 34071110
DOI: 10.3390/ijms22115500 -
Foods (Basel, Switzerland) Aug 2022The combination of two emulsifiers, lecithin and hydroxypropyl methylcellulose (HPMC), into emulsions is an interesting strategy to design fat replacers in food...
The combination of two emulsifiers, lecithin and hydroxypropyl methylcellulose (HPMC), into emulsions is an interesting strategy to design fat replacers in food matrices. The objective of this study was to investigate the effect of HPMC type and concentration on the formation, stability, and microstructure of conventional emulsions and nanoemulsions. Two different types of HPMC with low and high content of methyl and hydroxypropyl groups (HPMC-L and HPMC-H) were evaluated. The results showed that the molecular structure and concentration of HPMC play a major role in the viscoelastic behaviour, the gelation temperature, and the strength of gel formed. The firmness and work of shear of HPMC solutions increased significantly (p < 0.05) with increasing concentration. HPMC-L illustrated a more stable gel structure than the HPMC-H solution. Nanoemulsions showed lower moduli values, firmness, and work of shear than conventional emulsions due to the influence of high-pressure homogenization. A combination of lecithin and HPMC improved the physical and lipid oxidative stability of the emulsions, presenting a lower creaming index and thiobarbituric acid reactive substances (TBARS). In conclusion, HPMC-L at 2% w/w could be a suitable type and concentration combined with lecithin to formulate a saturated fat replacer that could mimic butter technological performance during food manufacturing operations.
PubMed: 36010537
DOI: 10.3390/foods11162536 -
The Journal of Clinical Investigation Feb 2022BACKGROUNDLong-term prognosis of WHO grade II low-grade gliomas (LGGs) is poor, with a high risk of recurrence and malignant transformation into high-grade gliomas.... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUNDLong-term prognosis of WHO grade II low-grade gliomas (LGGs) is poor, with a high risk of recurrence and malignant transformation into high-grade gliomas. Given the relatively intact immune system of patients with LGGs and the slow tumor growth rate, vaccines are an attractive treatment strategy.METHODSWe conducted a pilot study to evaluate the safety and immunological effects of vaccination with GBM6-AD, lysate of an allogeneic glioblastoma stem cell line, with poly-ICLC in patients with LGGs. Patients were randomized to receive the vaccines before surgery (arm 1) or not (arm 2) and all patients received adjuvant vaccines. Coprimary outcomes were to evaluate safety and immune response in the tumor.RESULTSA total of 17 eligible patients were enrolled - 9 in arm 1 and 8 in arm 2. This regimen was well tolerated with no regimen-limiting toxicity. Neoadjuvant vaccination induced upregulation of type-1 cytokines and chemokines and increased activated CD8+ T cells in peripheral blood. Single-cell RNA/T cell receptor sequencing detected CD8+ T cell clones that expanded with effector phenotype and migrated into the tumor microenvironment (TME) in response to neoadjuvant vaccination. Mass cytometric analyses detected increased tissue resident-like CD8+ T cells with effector memory phenotype in the TME after the neoadjuvant vaccination.CONCLUSIONThe regimen induced effector CD8+ T cell response in peripheral blood and enabled vaccine-reactive CD8+ T cells to migrate into the TME. Further refinements of the regimen may have to be integrated into future strategies.TRIAL REGISTRATIONClinicalTrials.gov NCT02549833.FUNDINGNIH (1R35NS105068, 1R21CA233856), Dabbiere Foundation, Parker Institute for Cancer Immunotherapy, and Daiichi Sankyo Foundation of Life Science.
Topics: Adult; Aged; CD8-Positive T-Lymphocytes; Cancer Vaccines; Carboxymethylcellulose Sodium; Female; Glioma; Humans; Male; Middle Aged; Neoadjuvant Therapy; Poly I-C; Polylysine; Tumor Microenvironment; Vaccination
PubMed: 34882581
DOI: 10.1172/JCI151239 -
Journal of Wound Care Sep 2021This study aimed to collect and analyse real-life data to characterise the initial use of Hydrofiber Technology dressings for the management of exuding wounds in France.
OBJECTIVE
This study aimed to collect and analyse real-life data to characterise the initial use of Hydrofiber Technology dressings for the management of exuding wounds in France.
METHOD
An online survey of nurses provided data from patients managed with two dressings-AQUACEL Extra or AQUACEL Ribbon-as the primary dressing. At baseline, sociodemographic data, relevant medical histories and wound characteristics were recorded. The status of the wounds was then examined on days seven and 14 of management, together with scores of both clinician and patient satisfaction.
RESULTS
The survey included 1093 patients with a mean age of 65.9 years, comprising 53.3% women; 615 (56.3%) patients presented with acute wounds and 478 with hard-to-heal wounds. Wounds were reported to have healed or improved in 79.4% and 88.1% of the patients after 7 and 14 days, respectively. After 14 days, the wounds were smaller (p<0.001), and the percentage of sloughy wound bed tissue had decreased (p<0.001), while the percentage of granulation tissue and epithelialisation increased significantly (p=0.024 and p=0.047, respectively). Tolerance of the dressing was good, with low levels of pain reported, both while wearing the dressing and on removal. On day 14, nurses reported a high level of satisfaction, while 70% and 42.7% of patients with acute and hard-to-heal wounds, respectively, were 'very satisfied'.
CONCLUSION
The Hydrofiber Technology dressings aided wound healing when used in the management of a wide range of acute and hard-to-heal wounds in medical and surgical indications. User satisfaction was high from both healthcare professionals and patients.
Topics: Aged; Bandages; Carboxymethylcellulose Sodium; Female; Granulation Tissue; Humans; Male; Patient Satisfaction; Wound Healing
PubMed: 34554834
DOI: 10.12968/jowc.2021.30.9.763